The primary focus of this investigation is to gain insight into the mechanism(s) responsible for the excessive prolactin (PRL) release associated with prolactin-secreting pituitary tumors. Studies will be performed in both normal and tumor-bearing rodent and human pituitaries in monolayer culture. We will seek dopaminergic defects in the control of PRL secretion in patients with prolactinomas. Patients with pituitary tumors will be given a low-dose dopamine infusion preoperatively and the response will be compared with the degree of inhibiton of PRL secretion obtained following dopamine administration to cultures of the pituitary tumor. A major emphasis of this evaluation will be to examine the influence of various calcium regulatory systems on PRL secretion in normal pituitary cultures and look for abnormalities in these systems in pituitary neoplasms. The importance of calcium influx, calmodulin and intracellular translocation of calcium in basal and stimulated PRL release will be evaluated. These effects on PRL secretion will be studied using calcium channel blockers, calmodulin inhibitors and scanning-transmission EM following cytochemical precipitation of calcium. The effect of these agents on adenyl cyclase and intracellular cAMP levels also will be assessed. These studies should provide further information concerning the normal control of pituitary PRL secretion as well as the characteristics on its release from transformed pituitary lactotrophs.